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Comprehensive model for formalized description,
visualization and simulation of biological systems
http://www.biouml.org
Fedor A. Kolpakov
Biosoft.Ru, Novosibirsk, Russia.
Design Technological Institute of Digital Techniques, Novosibirsk, Russia.
Sydney Brenner, 2002 Nobel Prize winner said:
"We now have unprecedented ability to collect data about nature
but there is now a crisis developing in biology, in that completely
unstructured information does not enhance understanding. We
need a framework to put all of this knowledge and data into —
that is going to be the problem in biology. We've reached the
stage where we can't talk to each other — we've all become
highly specialized. We need a framework, a framework where
people can come back to us and say, 'Yes, I understand.' Driving
toward that framework is really the big challenge."
BioUML – Biological Universal Modeling Language – is a step
in this direction. It is imagined as a language to write a “book of
life” i.e. model of the world in biological terms.
BioUML – Biological Universal Modeling Language – is open
source extensible Java workbench for modeling biological and
other complex systems. It spans the comprehensive range of
capabilities including access to databases with experimental data,
tools for formalized description of biological systems structure
and functioning, as well as tools for their visualization and
simulations.
Architecture overview
Standard module
GeneNet module
Diagram types
- Semantic map
- Pathway
- Pathway simulation
Database
Database adapter
KEGG/pathways
module
TRANSPATH
module
Java objects
Gene
Query engine
…
Protein
SBML module
Diagram
view part
Meta model
Graph structure
ModuleType
DiagramType
Executable model
-diagram types
-data categories
-query engine
-semantic controller
-diagram view builder
-diagram filter
Diagram
editor
Eclipse platform runtime
Analysis
tools
Diagram
editor part
Simulation
tools
Other
tools
Workbench UI
Perspectives
Views,
editors
Menus,
toolbars, etc.
Meta model
The core of BioUML workbench is meta model. It provides an
abstract layer for comprehensive formal description of wide
range of biological and other complex systems. Content of
databases on biological pathways or SBML models are
expressed in terms of meta model and then can be used by other
workbench plug-ins.
Meta model is problem domain neutral and splits the system
description into three interconnected levels:
1. graph structure - the system structure is described as
compartmentalized graph;
2. database level - each graph element can contain reference to
some database object;
3. executable model - any graph element can be element of
executable (mathematical) model, for example it can be variable
or equation.
Plug-ins are coded in Java. A typical plug-in consists of Java code in
a JAR library, some read-only files, and other resources such as
images, message catalogs, native code libraries, etc. BioUML
workbench installation includes a plugins folder where individual
plug-ins are deployed. Each plug-in is installed in its own folder
under the plugins folder. A plug-in is described in an XML manifest
file, called plugin.xml, residing in the plug-in's folder. The parsed
contents of plug-in manifest files are made available
programmatically through a plug-in registry API provided by Eclipse
runtime.
Example of formalized description of system from two chemical reactions
A
-k1[A] k1[A]
R1
100
ID A
CC ..
...
//
ID R1
A->B
...
//
A
100 -k1[A]
R1
B
0
ID B
CC ..
...
//
B
k1[A] 0
-k2[B] K2[B]
R2
ID R2
B->C
...
//
R2
-k2[B]
Special BioUML diagrams markup language (DML) is developed to
store BioUML meta model instance in XML format.
C
0
ID C
CC ..
...
//
C
K2[B] 0
Diagram structure description is divided into two parts:
Description of system
components in the
database
System structure is
described as a graph
Mathematical model
of the system
1) diagram structure model - it describes the graph structure,
location of diagram elements and database objects ('kernels') that are
associated with diagram elements.
2) executable model - stores mathematical model associated with
graph.
It is detailed description is available at:
http://www.biouml.org/dml.shtml
Standard BioUML module for biological pathways
BioUML workbench provides standard module for modeling
metabolic pathways, signal transduction pathways and gene
networks. The module defines most common biological data types
(gene, protein, RNA, substance, reaction, etc.), they mapping into
simple text database, query engine and three diagram types for
description of biological pathways on several semantic levels:
To take into account different diagram types and problem
domain specificity we have introduced the diagram type
concept. Diagram type defines:
· what system components can be shown in the diagram;
· diagram view builder - it allows to build graph view that take
into account problem domain peculiarity, for example
biological pathway diagram view builder uses specific views
for different pathway elements: proteins are shown as circles,
genes as rectangles, substances as squares, etc.;
· filters – hide or highlight diagram elements according to some
selection criteria, for example to according gene expression
specificity or expression level.
A plug-in is the smallest unit of BioUML workbench function that
can be developed and delivered separately into BioUML workbench.
Extension points are well-defined function points in the system
where other plug-ins can contribute functionality. An extension is a
specific contribution to an extension point. Plug-ins can define their
own extension points, so that other plug-ins can integrate tightly
with them.
Diagram markup language
Diagram type concept
· semantic controller - provides semantic integrity of the
diagram during its editing. It takes into account problem
domain constraints, for example if some specie is removed on
biological pathway diagram, all related reactions should be
removed too;
BioUML workbench is a plugin-based application framework that
provides its extensibility and possibility of seamless integration of
other tools for systems biology. It consists from a Eclipse platform
runtime kernel (http://www.eclipse.org) that supports 'plug-ins' and
a set of plug-ins that support database access, diagram editing, and
biological systems simulation.
1. Semantic network - this diagram type is used to describe
semantic relationships between system components, system states,
and related problem domain concepts. This diagram type is also
convenient as overview.
2. Pathway diagram type is used for formalized description of
biological pathway structure.
BioUML diagram view. GeneNet database was incorporated into
BioUML as GeneNet module; central pane shows “Antiviral response”
diagram; right top pane shows filters that are applied to the diagram. The
data are taken from the publicly available version of GeneNet database.
Module concept
3. Pathway simulation diagram type is extension of pathway
structure diagram, where variables are associated with graph nodes
and differential equations with graph edges. This allows to
BioUML workbench automatically generate mathematical model
of the system and simulate its dynamics.
Availability
BioUML workbench (including source code) is freely available at
http://www.biouml.org
The module concept allows to developer define new diagram
types and incorporate other databases on biological pathways
into BioUML framework.
There is special forum dedicated to BioUML workbench where you
can post your questions and suggestions. We really needs in your
feedback.
The module defines mapping of database content into diagram
elements and diagram types that can be used with the
database.Module also provides query engine that can be used by
BioUML framework ti find interactiong components of the
system. Search results can be shown as graph and edited by user.
http://groups.yahoo.com/group/biouml/
Acknowledgments
Part of this work was partially supported by the grant of
Volkswagen-Stiftung (I/75941).
Modules:
· standard BioUML module for biological pathways;
· module for models in SBML format;
· module for GeneNet database;
· module for KEGG/Pathways datbase;
· module for TRANSPATH database.
Author is grateful to Alexander Kel and Sergey Zhatchenko for
useful comments and discussions, as well as to Igor Tyazhev, Vlad
Zhvaleev and Oleg Onegov for technical support.
Example of seach using GenNet module query engine and results
visulisation by BioUML workbench.